title: Human placental mesenchymal stem cells (pMSCs) play a role as immune suppressive cells by shifting macrophage differentiation from inflammatory M1 to anti-inflammatory M2 macrophages.
abstract: BACKGROUND
  Mesenchymal stem cells (MSCs) have a therapeutic potential in tissue repair because of capacity for multipotent differentiation and their ability to modulate the immune response. In this study, we examined the ability of human placental MSCs (pMSCs) to modify the differentiation of human monocytes into macrophages and assessed the influence of pMSCs on important macrophage functions.
  
  
  METHODS
  We used GM-CSF to stimulate the differentiation of monocytes into the M1 macrophage pathway and then co-cultured these cells with pMSCs in the early stages of macrophage differentiation. We then evaluated the effect on differentiation by microscopic examination and by quantification of molecules important in the differentiation and immune functions of macrophages using flow cytometry and ELISA. The mechanism by which pMSCs could mediate their effects on macrophage differentiation was also studied.
  
  
  RESULTS
  The co-culture of pMSCs with monocytes stimulated to follow the inflammatory M1 macrophage differentiation pathway resulted in a shift to anti-inflammatory M2-like macrophage differentiation. This transition was characterized by morphological of changes typical of M2 macrophages, and by changes in cell surface marker expression including CD14, CD36, CD163, CD204, CD206, B7-H4 and CD11b, which are distinctive of M2 macrophages. Co-culture with pMSCs reduced the expression of the costimulatory molecules (CD40, CD80 and CD86) and increased the expression of co-inhibitory molecules (CD273, CD274 and B7-H4) as well as the surface expression of major histocompatibility complex (MHC-II) molecules. Furthermore, the secretion of IL-10 was increased while the secretion of IL-1β, IL-12 (p70) and MIP-1α was decreased; a profile typical of M2 macrophages. Finally, pMSCs induced the phagocytic activity and the phagocytosis of apoptotic cells associated with M2- like macrophages; again a profile typical of M2 macrophages. We found that the immunoregulatory effect of pMSCs on macrophage differentiation was mediated by soluble molecules acting partially via glucocorticoid and progesterone receptors.
  
  
  CONCLUSIONS
  We have shown that pMSCs can transition macrophages from an inflammatory M1 into an anti-inflammatory M2 phenotype. Our findings suggest a new immunosuppressive property of pMSCs that may be employed in the resolution of inflammation associated with inflammatory diseases and in tissue repair.
authors.affiliation: College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, National Guard Health Affairs, P.O. Box 22490, Riyadh, 11426, Mail Code 1515, Saudi Arabia, mohamedabumaree@hotmail.com.
authors.forename: M H
authors.initials: MH
authors.lastname: Abumaree
authors.forename: M A
authors.initials: MA
authors.lastname: Al Jumah
authors.forename: B
authors.initials: B
authors.lastname: Kalionis
authors.forename: D
authors.initials: D
authors.lastname: Jawdat
authors.forename: A
authors.initials: A
authors.lastname: Al Khaldi
authors.forename: F M
authors.initials: FM
authors.lastname: Abomaray
authors.forename: A S
authors.initials: AS
authors.lastname: Fatani
authors.forename: L W
authors.initials: LW
authors.lastname: Chamley
authors.forename: B A
authors.initials: BA
authors.lastname: Knawy
mesh_terms: D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D003571:Cytochalasin B / Q000276:immunology / Q000494:pharmacology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology; D010920:Placenta / Q000166:cytology; D011247:Pregnancy
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D003571:Cytochalasin B; D016178:Granulocyte-Macrophage Colony-Stimulating Factor